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https://www.readbyqxmd.com/read/29097160/clinical-practice-guidelines-for-diagnosis-and-treatment-of-chronic-lymphocytic-leukemia-cll-in-the-netherlands
#1
Sabina Kersting, Suzanne I M Neppelenbroek, Hein P J Visser, Michel van Gelder, Mark-David Levin, Rogier Mous, Ward Posthuma, Hanneke M van der Straaten, Arnon P Kater
INTRODUCTION: In recent years, considerable progress has been made in the treatment of patients with chronic lymphocytic leukemia (CLL), and new potent drugs have become available. Therefore, the CLL working party revised the Dutch guidelines. Not only efficacy but also quality of life and socio-economic impact were taken into account in the formulation of treatment recommendations. MATERIALS AND METHODS: The working party discussed a set of questions regarding diagnostic tests and treatment and wrote the draft guideline...
September 25, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29082795/treatment-approach-for-elderly-and-unfit-patients-with-chronic-lymphocytic-leukemia
#2
Idanna Innocenti, Francesco Autore, Raffaella Pasquale, Francesca Morelli, Dimitar G Efremov, Luca Laurenti
Elderly patients with chronic lymphocytic leukemia (CLL) or patients with comorbidities are often treated with chlorambucil (Chl) as front-line therapy despite relatively low response rates. The addition of a monoclonal anti-CD20 antibody to Chl substantially increases response rates and prolongs progression-free survival (PFS) in these patients, without increasing toxicity. As a result, the ESMO guidelines recommend that previously untreated CLL patients with relevant co-morbidity, but without TP53 deletion/mutation, should be treated with the combination of Chl plus an anti-CD20 antibody (rituximab, ofatumumab or obinutuzumab)...
October 30, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28958786/-lymphomas-a-therapeutic-update
#3
REVIEW
A Wolfromm, R Delarue
Emergence of new molecules has considerably reshaped the management of patients in onco-hematology. Cytotoxic chemotherapy has not been altered, and CHOP remains the reference treatment for lymphomas. However, the development of targeted therapies has allowed for a broader spectrum of treatments. Immunotherapy with monoclonal antibodies entered the market with rituximab in diffuse large B-cell lymphomas, in the 1990s and it is now developing as new-generation anti-CD20 antibodies (obinotuzumab and ofatumumab)...
October 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28922238/primary-central-nervous-system-lymphoma-time-for-diagnostic-biomarkers-and-biotherapies
#4
Louis Royer-Perron, Khê Hoang-Xuan, Agusti Alentorn
PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare cancer with a somber prognosis in older patients, which it affects predominantly. Only in recent years have molecular alterations characterizing PCNSL been thoroughly described. This opens possibilities for the use of targeted therapies. Developments in imaging and biomarkers have also great potential to help clinicians faced with diagnostic and prognostic uncertainties. RECENT FINDINGS: Several biomarkers for PCNSL, such as different microRNAs, which could be tested in cerebrospinal fluid and vitreous fluid, and IL-10, which has been shown to have excellent sensitivity and specificity in the cerebrospinal fluid, have emerged in the last years...
September 15, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28715249/durable-molecular-remissions-in-chronic-lymphocytic-leukemia-treated-with-cd19-specific-chimeric-antigen-receptor-modified-t-cells-after-failure-of-ibrutinib
#5
Cameron J Turtle, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, Sindhu Cherian, Xueyan Chen, Brent Wood, Arletta Lozanski, John C Byrd, Shelly Heimfeld, Stanley R Riddell, David G Maloney
Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 × 10(5), 2 × 10(6), or 2 × 10(7) CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib...
September 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#6
MULTICENTER STUDY
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28278728/soluble-cd52-is-an-indicator-of-disease-activity-in-chronic-lymphocytic-leukemia
#7
Fie J Vojdeman, Sarah E M Herman, Nikolai Kirkby, Adrian Wiestner, Mars B van T' Veer, Geir E Tjønnfjord, Maija A Itälä-Remes, Eva Kimby, Mohammed Z Farooqui, Aaron Polliack, Ka Lung Wu, Jeanette K Doorduijn, Wendimagegn G Alemayehu, Shulamiet Wittebol, Tomas Kozak, Jan Walewski, Martine C J Abrahamse-Testroote, Marinus H J van Oers, Christian H Geisler, Carsten U Niemann
CD52 is a glycoprotein expressed on normal as well as leukemic immune cells and shed as soluble CD52 (sCD52). We studied sCD52 levels in three CLL cohorts: the 'early', the 'high-risk', and the 'ibrutinib-treated'. The 'high-risk' patients had significantly higher sCD52 levels than the 'early' patients. For the 'early' patients, high sCD52 levels were associated with a significantly shorter time to first treatment. Regarding prognostic factors, no clear correlations with stage, IGHV, or beta-2-microglobulin were found; in a cox multivariate analysis of the 'early' patients, sCD52 and IGHV both had independent prognostic value...
February 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28140709/recent-advances-and-future-directions-in-mantle-cell-lymphoma-research-report-of-the-2016-mantle-cell-lymphoma-consortium-workshop
#8
Brad S Kahl, Martin Dreyling, Leo I Gordon, Leticia Quintanilla-Martinez, Eduardo M Sotomayor
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma typically associated with the t(11;14) chromosomal translocation, resulting in overexpression of cyclin D1. Although MCL is associated with clinical heterogeneity, outcomes are generally poor and no standard treatment has been established. However, the recent approval of ibrutinib provides a new therapeutic option. Moreover, recent clinical trials have provided new perspectives on the relative efficacy and safety of various approaches for both transplant-eligible and transplant-ineligible patients...
July 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27825466/current-therapy-guidelines-for-waldenstrom-s-macroglobulinaemia
#9
REVIEW
Efstathios Kastritis, Meletios A Dimopoulos
Waldenstrom's macroglobulinaemia (WM) is a B-cell neoplasm in which bone marrow is infiltrated by lymphoplasmacytic cells that secrete monoclonal immunoglobulin M (IgM). More than a decade ago, specific criteria were agreed to define diagnosis and symptomatic disease requiring therapy; however, treatment recommendations change as new options emerge. Treatment decisions consider specific disease characteristics (burden of disease, IgM levels, presence of cytopenias) and patient characteristics (age, comorbidities, toxicity)...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27432877/treatment-recommendations-from-the-eighth-international-workshop-on-waldenstr%C3%A3-m-s-macroglobulinemia
#10
REVIEW
Véronique Leblond, Efstathios Kastritis, Ranjana Advani, Stephen M Ansell, Christian Buske, Jorge J Castillo, Ramón García-Sanz, Morie Gertz, Eva Kimby, Charalampia Kyriakou, Giampaolo Merlini, Monique C Minnema, Pierre Morel, Enrica Morra, Mathias Rummel, Ashutosh Wechalekar, Christopher J Patterson, Steven P Treon, Meletios A Dimopoulos
Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of the International Workshop on Waldenström's Macroglobulinemia (IWWM). At IWWM-8, a task force for treatment recommendations was impanelled to review recently published and ongoing clinical trial data as well as the impact of new mutations (MYD88 and CXCR4) on treatment decisions, indications for B-cell receptor and proteasome inhibitors, and future clinical trial initiatives for WM patients...
September 8, 2016: Blood
https://www.readbyqxmd.com/read/26988407/chronic-lymphocytic-leukemia-therapy-new-targeted-therapies-on-the-way
#11
REVIEW
Candida Vitale, Jan A Burger
INTRODUCTION: The critical role of the tissue microenvironment and B-cell receptor (BCR) signaling in chronic lymphocytic leukemia (CLL) pathogenesis, and the clinical success of targeted agents that disrupt BCR signaling are currently changing the CLL landscape. Three new drugs were recently approved for CLL therapy, and other agents are in late development. AREAS COVERED: In this review, we summarize data on promising new targeted drugs for CLL. The heterogeneous mechanisms of actions of these molecules are described, such as the inhibition of BCR signaling, direct targeting of CD20 molecules on the CLL cell surface, and BCL-2 inhibition...
June 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/26690614/chronic-lymphocytic-leukemia-cll-then-and-now
#12
REVIEW
Kanti R Rai, Preetesh Jain
The field of chronic lymphocytic leukemia (CLL) has witnessed considerable change since the time clinical staging was introduced in clinical practice in 1975. Over the years, the prognostication in CLL has expanded with the addition in late 90s of mutational status of variable region of immunoglobulin heavy chain (IGHV), and chromosomal analyses using fluorescent in situ hybridization (FISH). More recently, stereotypy of BCR (B cell receptor) and whole exome sequencing (WES) based discovery of specific mutations such as NOTCH1, TP53, SF3B1, XPO-1, BIRC3, ATM, and RPS15 further refined the current prognostication system in CLL...
March 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/26637744/management-of-prolymphocytic-leukemia
#13
Claire Dearden
B-cell (B-PLL) and T-cell (T-PLL) prolymphocytic leukemias are rare, poor-prognosis lymphoid neoplasms with similar presentation characterized by symptomatic splenomegaly and lymphocytosis. They can be distinguished from each other and from other T- and B-cell leukemias by careful evaluation of morphology, immunophenotyping, and molecular genetics. The clinical behavior is typically aggressive, although a subset of patients may have an indolent phase of variable length. First-line therapy for T-PLL is with intravenous alemtuzumab and for B-PLL is with combination purine analog-based chemo-immunotherapy...
2015: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/26337639/blinatumomab-a-bispecific-t-cell-engager-bite-antibody-against-cd19-cd3-for-refractory-acute-lymphoid-leukemia
#14
REVIEW
Jingjing Wu, Jiaping Fu, Mingzhi Zhang, Delong Liu
Targeted therapy has been the forefront of cancer treatment. Cancer immunotherapy is the most recent focus. In addition, novel immunotherapeutics targeting B cell receptor signaling (e.g., ibrutinib), T cell receptor ( e.g., CART19), and NK cells (e.g., AFM13) are being developed. This review summarized the new development in blinatumomab (MT103/MEDI-538), a first-in-class bispecific T engager (BiTE) antibody against CD19/CD3 in patients with relapsed/refractory precursor B cell acute lymphoid leukemia.
September 4, 2015: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/26150724/a-critical-appraisal-of-ibrutinib-in-the-treatment-of-mantle-cell-lymphoma-and-chronic-lymphocytic-leukemia
#15
REVIEW
David L Tucker, Simon A Rule
Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in-class, oral inhibitor of Bruton's tyrosine kinase, which functions by irreversible inhibition of the downstream signaling pathway of the B-cell receptor, which normally promotes cell survival and proliferation...
2015: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/25201956/evolution-of-ibrutinib-resistance-in-chronic-lymphocytic-leukemia-cll
#16
Natalia L Komarova, Jan A Burger, Dominik Wodarz
The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib is a new targeted therapy for patients with chronic lymphocytic leukemia (CLL). Ibrutinib is given orally on a continuous schedule and induces durable remissions in the majority of CLL patients. However, a small proportion of patients initially responds to the BTKi and then develops resistance. Estimating the frequency, timing, and individual risk of developing resistance to ibrutinib, therefore, would be valuable for long-term management of patients. Computational evolutionary models, based on measured kinetic parameters of patients, allow us to approach these questions and to develop a roadmap for personalized prognosis and treatment management...
September 23, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25048786/immunomodulation-and-immune-reconstitution-in-chronic-lymphocytic-leukemia
#17
REVIEW
John C Riches, John G Gribben
Over the past decade, there have been significant advances in our understanding of the pathogenesis of chronic lymphocytic leukemia (CLL), which has been accompanied by an explosion in treatment options. Although the combination of fludarabine, cyclophosphamide, and rituximab is the current frontline treatment of choice for fit patients, targeted therapies such ibrutinib, idelalisib, and ABT-199 are showing great promise in clinical trials. However, none of these drugs seems curative, and allogeneic hematopoietic stem cell transplantation remains the only strategy that produces durable clinical remissions in otherwise poor-risk disease...
July 2014: Seminars in Hematology
https://www.readbyqxmd.com/read/24893041/unmet-needs-in-the-treatment-of-mantle-cell-lymphoma
#18
REVIEW
Steven T Rosen, Brian K Link, Nathan H Fowler
Mantle cell lymphoma is one of the most challenging hematologic malignancies, owing to an aggressive disease course, a high rate of relapse, and lack of standard of care. In the United States, mantle cell lymphoma accounts for approximately 6% of all newly diagnosed cases of non-Hodgkin lymphoma. Because most patients are initially diagnosed with advanced-stage disease, they are often symptomatic at presentation. Common features include widespread lymphadenopathy and splenomegaly, as well as bone marrow infiltration...
November 2013: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/24693884/different-sensitivity-of-germinal-center-b-cell-like-diffuse-large-b-cell-lymphoma-cells-towards-ibrutinib-treatment
#19
Xiaohui Zheng, Ning Ding, Yuqin Song, Lixia Feng, Jun Zhu
BACKGROUND: Although rituximab in the combination of CHOP chemotherapy has been widely used as the standard treatment for several kinds of B-cell non-Hodgkin lymphoma (B-NHL), a great number of B-NHL patients treated with this immunotherapy still develop primary and secondary resistance. Recently Bruton's tyrosine kinase (Btk) inhibitor ibrutinib showed promising therapeutic effect in relapsed/refractory CLL and B-cell NHL, which provided essential alternatives for these patients. METHODS: The proliferation and apoptosis induction of tumor cells were measured by cell viability assay and Annexin-V staining...
2014: Cancer Cell International
https://www.readbyqxmd.com/read/24157582/immunotherapy-for-chronic-lymphocytic-leukemia-in-the-era-of-btk-inhibitors
#20
REVIEW
M A Kharfan-Dabaja, W G Wierda, L J N Cooper
Understanding the pathogenesis of CLL has uncovered a plethora of novel targets for human application of monoclonal antibodies, engineered T cells, or inhibitors of signal transduction pathways. The B-cell receptor signaling pathway is being actively explored as a therapeutic target in CLL. Ibrutinib, an inhibitor of Bruton's tyrosine kinase is showing impressive responses in heavily pre-treated high-risk CLL, whether alone or in combination with MoAbs or chemotherapy. Other key components of the BCR pathway, namely PI3K-δ, are also being targeted with novel therapies with promising results as well...
March 2014: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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